To the Editor,
The final goal of transplant physicians is the induction of donor-specific tolerance (DST), in which the host permanently accepts the graft, but immunity against other antigens is maintained. There have been reports of successful induction of DST in rodent models. However, the majority of studies have focused primarily on the inhibition of co-stimulatory signals that regulate the activation of T cells, and belatacept, a high-affinity variant of CTLA4-IgG, is the only biological drug that has been applied to human organ transplantation [1]. Antigen-presenting cells (APCs) are activated by the innate immune response, and mature APCs are the key regulators of rejection through activation of the acquired immune response. Therefore, the control of APC maturation is the key step in induction of DST in the field of organ transplantation. Previously, we reported induction of DST through control of APC maturation [2]. However, we were not able to delineate the underlying mechanisms, nor apply the methods to other models of transplantation.
Recently, Jung et al. [3] reported a significant contribution where they showed successful induction of DST through the control of APC maturation. They developed a way to maintain APCs in a semi-arrested state by administration of an antibody ligating a particular epitope on intercellular adhesion molecule 1 (ICAM-1). Signaling through ICAM-1 is important for the activation of APCs. They evaluated the effect of semi-arrested APCs on xenogeneic grafts in humanized mice and non-human primates. Thus, they provided a feasible method that may assist the realization of the DST concept. Further work will likely be connected to clinical trials.
However, care should be taken when interpreting these results and applying them directly to humans. The study was performed not on 'organs' but, rather, on a 'group of cells', because 'group of cells' induces a milder immune response, as compared to that against an organ. Moreover, a thorough method for screening various microorganisms in xenogeneic species has not yet been developed. Therefore, the safety issue remains to be resolved. Despite these limitations, this study provides new insight and will help overcome the problem of non-specific immunosuppression. Furthermore, this study may facilitate control of immune responses more meticulously and safely by providing a method of controlling the immune response at the site of interest.
Secondary rapidly progressive glomerulonephritis (RPGN) can be caused by many diseases and conditions, including vasculitis, systemic rheumatic diseases, infections, drugs and malignancies.Among the secondary RPGNs, malignancy-associated RPGN is extremely rare and causes renal function deterioration within several weeks to months.Thus, timely immunosuppressant therapy can improve renal outcome.Herein, we describe a case of RPGN detected simultaneously with marginal zone B-cell lymphoma.An 82-year-old male patient, who presented generalized edema and oliguria, was diagnosed with crescentic glomerulonephritis and marginal B-cell lymphoma.After the patient was given methylprednisolone pulse therapy, renal function was restored and hemodialysis was successfully discontinued without complications.(
Abstract A multicenter cohort study. The DialysisNet was previously developed for the management of hemodialysis (HD) patients based on the American Society for Testing and Materials Continuity of Care Records by metadata transformation. DialysisNet is a dialysis patient management program created by using the personal health record care platform to overcome the problems of registry studies, in real-time. Here, we aimed to investigate the pattern of treatment for renal anemia in HD patients using DialysisNet. We performed a multicenter cohort study among HD patients who were treated at one of the three Korean university-affiliated hospitals from January 2016 to December 2016. Subjects were divided into 4 hemoglobin variability groups by quartiles. The variable anemia treatment pattern was reviewed. To determine renal anemia treatment patterns, we automatically collected information on the practice of anemia treatment patterns such as erythropoietin stimulating agent (ESA) doses and administration frequencies, and targeted hemoglobin maintenance rate. Individual hemoglobin variabilities were expressed as (standard deviations)/(√(n/[n–1]). The records of 159 patients were analyzed (Hospital A: 35, Hospital B: 21, Hospital C: 103). Mean patients’ age was 65.6 ± 12.8 years, and 61.6% were men. Overall, hemoglobin level was 10.5[7.43;13.93] g/dL. 158 (99.3%) patients were using ESA; and overall, the epoetin alfa dose was 33,000[4000;136,800] U per week. Hemoglobin levels ( P = .206) and epoetin alfa doses were similar ( P = .924) for patients with different hemoglobin variabilities. The hemoglobin target maintenance rate was lower in the highest hemoglobin variability group than in the lowest variability group ( P = .045). In this study, detailed information on the actual anemia treatment patterns were obtained using the DialysisNet. We expect that DialysisNet will simplify and improve the renal anemia management for both dialysis patients and health care providers.
Evaluation of the retinal nerve fibre layer (RNFL) is important for identifying glaucomatous damage. Ultrawide-field fundus photography (UWP) imaging is increasingly used in the ophthalmological field; however, it is unknown whether it can be used for detecting RNFL defects (RNFLDs). We investigated whether RNFLD can be detected with UWP images and compared the clinical effectiveness of three types of images for detecting RNFLD: conventional red-free RNFL photography (RFP), non-mydriatic UWP and digitally converted green separation of non-mydriatic UWP (G-UWP).Eyes with glaucoma or glaucoma suspect and normal control eyes meeting the eligibility criteria were consecutively enrolled from September 2019 to April 2020. Their conventional RFP, non-mydriatic UWP and G-UWP images were assessed for detecting RNFLD to evaluate the sensitivity and specificity for detecting RNFLD.Three image sets of 196 participants (84 normal control, 25 glaucoma suspect and 87 glaucoma) were obtained. The sensitivity of G-UWP (94.6%; 95% CI 88.7 to 98.0) and RFP (92.9%; 95% CI 86.4 to 96.9) was higher than that of UWP (82.1%; 95% CI 73.8 to 88.7; p<0.05). The sensitivities of G-UWP and RFP are comparable. The specificity of G-UWP (78.6%; 95% CI 68.3 to 86.8) and UWP (75.0%; 95% CI 64.4 to 83.8) was comparable, but both were lower than that of RFP (98.8%; 95% CI 93.5 to 100.0; p<0.05).Non-mydriatic UWP images can be used to detect RNFLD. Non-mydriatic G-UWP showed comparable sensitivity but lower specificity to conventional RFP. Non-mydriatic G-UWP could be used as a convenient and useful diagnostic tool for screening glaucoma in clinical settings.
Abstract Central serous chorioretinopathy (CSC) is a common condition characterized by serous detachment of the neurosensory retina at the posterior pole. We built a deep learning system model to diagnose CSC, and distinguish chronic from acute CSC using spectral domain optical coherence tomography (SD-OCT) images. Data from SD-OCT images of patients with CSC and a control group were analyzed with a convolutional neural network. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUROC) were used to evaluate the model. For CSC diagnosis, our model showed an accuracy, sensitivity, and specificity of 93.8%, 90.0%, and 99.1%, respectively; AUROC was 98.9% (95% CI, 0.983–0.995); and its diagnostic performance was comparable with VGG-16, Resnet-50, and the diagnoses of five different ophthalmologists. For distinguishing chronic from acute cases, the accuracy, sensitivity, and specificity were 97.6%, 100.0%, and 92.6%, respectively; AUROC was 99.4% (95% CI, 0.985–1.000); performance was better than VGG-16 and Resnet-50, and was as good as the ophthalmologists. Our model performed well when diagnosing CSC and yielded highly accurate results when distinguishing between acute and chronic cases. Thus, automated deep learning system algorithms could play a role independent of human experts in the diagnosis of CSC.
Background: Recent reports have suggested the possible benefit of beginning hemodialysis (HD) at a rate less frequent than three times weekly and incrementally increasing the dialysis dose. However, the data regarding the benefits and safety of incremental HD are insufficient. Methods: We analyzed 927 patients with newly initiated HD from the Clinical Research Center for End-Stage Renal Disease cohort from 2008 to 2014. The patients were classified into a thrice-weekly initiation group or an incremental initiation group (one to two sessions per week) according to the frequency of HD per week at baseline. We compared health-related quality of life (HRQOL), daily urine volume at 12 months and all-cause mortality between the groups. We matched the thrice-weekly and incremental groups at a 1:2 ratio using propensity score matching. Results: A total of 312 patients (207 in the thrice-weekly group and 105 in the incremental group) were selected. All-cause mortality was comparable between the two groups before and after propensity score matching. The HRQOL tended to be better in the incremental group for the majority of domains of the Kidney Disease Quality of Life Short Form and Beck's Depression Inventory; however, only the symptoms and problems domain was significantly better in the incremental group at 3 months after HD. At 12 months after HD, there were no differences between the groups. The daily urine volume at 12 months after HD was similar between the two groups. Conclusions: Incremental HD initiation showed comparable results to thrice-weekly initiation for HRQOL, residual renal function and all-cause mortality. Incremental HD may be considered an additional option for HD initiation in selected patients.
Abstract This cross-sectional study aimed to build a deep learning model for detecting neovascular age-related macular degeneration (AMD) and to distinguish retinal angiomatous proliferation (RAP) from polypoidal choroidal vasculopathy (PCV) using a convolutional neural network (CNN). Patients from a single tertiary center were enrolled from January 2014 to January 2020. Spectral-domain optical coherence tomography (SD-OCT) images of patients with RAP or PCV and a control group were analyzed with a deep CNN. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUROC) were used to evaluate the model’s ability to distinguish RAP from PCV. The performances of the new model, the VGG-16, Resnet-50, Inception, and eight ophthalmologists were compared. A total of 3951 SD-OCT images from 314 participants (229 AMD, 85 normal controls) were analyzed. In distinguishing the PCV and RAP cases, the proposed model showed an accuracy, sensitivity, and specificity of 89.1%, 89.4%, and 88.8%, respectively, with an AUROC of 95.3% (95% CI 0.727–0.852). The proposed model showed better diagnostic performance than VGG-16, Resnet-50, and Inception-V3 and comparable performance with the eight ophthalmologists. The novel model performed well when distinguishing between PCV and RAP. Thus, automated deep learning systems may support ophthalmologists in distinguishing RAP from PCV.
Abstract Background Renal failure is one of the most serious complications associated with autosomal dominant polycystic kidney disease (ADPKD). To date, early markers have failed to predict renal function deterioration at the early stages. This 1-year prospective study evaluated N-acetyl-β-D-glucosaminidase (NAG) as a new surrogate marker for renal function in ADPKD. Methods A total of 270 patients were enrolled in the study, and we measured urinary NAG, β2-microglobulin, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) prospectively for 1 year to compare their predictive values for renal function. Results Baseline urinary NAG/Cr was negatively correlated with estimated glomerular filtration rate (GFR) ( r 2 = 0.153, P < 0.001) and positively correlated with total kidney volume (TKV) ( r 2 = 0.113, P < 0.001). Among other biomarkers, urinary NAG/Cr better discriminated patients with decreased renal function from those with conserved renal function, showing the largest area under the curve (AUC 0.794). Immunohistochemical study revealed strong staining along the cyst-lining epithelial cells as well as the nearby compressed tubular epithelial cells. However, both single and repeated measurements of urinary NAG/Cr failed to predict renal function decline in 1 year. Conclusions Urinary NAG/Cr may be a useful surrogate marker for renal function in ADPKD patients.
'%3e%3cg id='b'%3e%3cpath id='a' stroke='%23000' stroke-width='2' d='M-6-25H6m-12 3H6m-12 3H6'/%3e%3cuse xlink:href='%23a' y='44'/%3e%3c/g%3e%3cpath stroke='%23fff' d='M0 17v10'/%3e%3ccircle r='12' fill='%23cd2e3a'/%3e%3cpath fill='%230047a0' d='M0-12A6 6 0 0 0 0 0a6 6 0 0 1 0 12 12 12 0 0 1 0-24z'/%3e%3c/g%3e%3cg transform='rotate(-123.69)'%3e%3cuse xlink:href='%23b'/%3e%3cpath stroke='%23fff' d='M0-23.5v3M0 17v3.5m0 3v3'/%3e%3c/g%3e%3c/svg%3e)
'%3e%3ccircle r='120' fill='%230f47af'/%3e%3cg id='a'%3e%3cpath fill='%23fcdd09' d='m0-96-4.206 12.944 17.348 53.39h-23.13l-2.599 8h74.163l11.011-8H21.553z'/%3e%3cpath stroke='%23fcdd09' stroke-width='4' d='m25.863-35.597 30.564-42.069'/%3e%3c/g%3e%3cuse xlink:href='%23a' transform='rotate(72)'/%3e%3cuse xlink:href='%23a' transform='rotate(144)'/%3e%3cuse xlink:href='%23a' transform='rotate(216)'/%3e%3cuse xlink:href='%23a' transform='rotate(288)'/%3e%3c/g%3e%3c/svg%3e)